Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome

Roderick F A de Lind van Wijngaarden; Elbrich P C Siemensma; Dederieke A M Festen; Barto J Otten; Edgar G A H van Mil; Joost Rotteveel; Roelof J H Odink; G C B Karen Bindels-de Heus; Mariëtte van Leeuwen; Danny A J P Haring; Gianni Bocca; E C A Mieke Houdijk; J J Gera Hoorweg-Nijman; René C F M Vreuls; Petr E Jira; A S Paul van Trotsenburg; Boudewijn Bakker; Eelco J Schroor; Jan Willem Pilon; Jan M Wit; Stenvert L S Drop; Anita C S Hokken-Koelega

doi:10.1210/jc.2009-0454

Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome

Roderick F A de Lind van Wijngaarden^*
, Elbrich P C Siemensma
, Dederieke A M Festen
, Barto J Otten
, Edgar G A H van Mil
, Joost Rotteveel
, Roelof J H Odink
, G C B Karen Bindels-de Heus
, Mariëtte van Leeuwen
, Danny A J P Haring
, Gianni Bocca
, E C A Mieke Houdijk
, J J Gera Hoorweg-Nijman
, René C F M Vreuls
, Petr E Jira
, A S Paul van Trotsenburg
, Boudewijn Bakker
, Eelco J Schroor
, Jan Willem Pilon
, Jan M Wit

Stenvert L S Drop, Anita C S Hokken-Koelega

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects.

OBJECTIVES: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters.

SETTING: We conducted a multicenter prospective trial.

DESIGN: Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)).

RESULTS: Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids.

CONCLUSIONS: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.

Original language	English
Pages (from-to)	4205-15
Number of pages	11
Journal	Journal of Clinical Endocrinology & Metabolism
Volume	94
Issue number	11
DOIs	https://doi.org/10.1210/jc.2009-0454
Publication status	Published - Nov 2009
Externally published	Yes

Keywords

Adipose Tissue/anatomy & histology
Birth Weight
Blood Pressure
Body Height
Body Weight
Bone Density
Child
Child, Preschool
Drug Administration Schedule
Fasting
Human Growth Hormone/administration & dosage
Humans
Insulin-Like Growth Factor Binding Protein 3/blood
Insulin-Like Growth Factor I/metabolism
Prader-Willi Syndrome/drug therapy
Prospective Studies
Safety

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10.1210/jc.2009-0454

http://hdl.handle.net/1765/25377Licence: Other

Cite this

de Lind van Wijngaarden, R. F. A., Siemensma, E. P. C., Festen, D. A. M., Otten, B. J., van Mil, E. G. A. H., Rotteveel, J., Odink, R. J. H., Bindels-de Heus, G. C. B. K., van Leeuwen, M., Haring, D. A. J. P., Bocca, G., Houdijk, E. C. A. M., Hoorweg-Nijman, J. J. G., Vreuls, R. C. F. M., Jira, P. E., van Trotsenburg, A. S. P., Bakker, B., Schroor, E. J., Pilon, J. W., ... Hokken-Koelega, A. C. S. (2009). Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome. Journal of Clinical Endocrinology & Metabolism, 94(11), 4205-15. https://doi.org/10.1210/jc.2009-0454

@article{8069f969a27940e0a850dce92678ed7e,

title = "Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome",

abstract = "BACKGROUND: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects.OBJECTIVES: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters.SETTING: We conducted a multicenter prospective trial.DESIGN: Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat\%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)).RESULTS: Fat\%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids.CONCLUSIONS: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat\%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.",

keywords = "Adipose Tissue/anatomy \& histology, Birth Weight, Blood Pressure, Body Height, Body Weight, Bone Density, Child, Child, Preschool, Drug Administration Schedule, Fasting, Human Growth Hormone/administration \& dosage, Humans, Insulin-Like Growth Factor Binding Protein 3/blood, Insulin-Like Growth Factor I/metabolism, Prader-Willi Syndrome/drug therapy, Prospective Studies, Safety",

author = "\{de Lind van Wijngaarden\}, \{Roderick F A\} and Siemensma, \{Elbrich P C\} and Festen, \{Dederieke A M\} and Otten, \{Barto J\} and \{van Mil\}, \{Edgar G A H\} and Joost Rotteveel and Odink, \{Roelof J H\} and \{Bindels-de Heus\}, \{G C B Karen\} and \{van Leeuwen\}, Mari{\"e}tte and Haring, \{Danny A J P\} and Gianni Bocca and Houdijk, \{E C A Mieke\} and Hoorweg-Nijman, \{J J Gera\} and Vreuls, \{Ren{\'e} C F M\} and Jira, \{Petr E\} and \{van Trotsenburg\}, \{A S Paul\} and Boudewijn Bakker and Schroor, \{Eelco J\} and Pilon, \{Jan Willem\} and Wit, \{Jan M\} and Drop, \{Stenvert L S\} and Hokken-Koelega, \{Anita C S\}",

year = "2009",

month = nov,

doi = "10.1210/jc.2009-0454",

language = "English",

volume = "94",

pages = "4205--15",

journal = "Journal of Clinical Endocrinology \& Metabolism",

issn = "0021-972X",

publisher = "Endocrine Society",

number = "11",

}

de Lind van Wijngaarden, RFA, Siemensma, EPC, Festen, DAM, Otten, BJ, van Mil, EGAH, Rotteveel, J, Odink, RJH, Bindels-de Heus, GCBK, van Leeuwen, M, Haring, DAJP, Bocca, G, Houdijk, ECAM, Hoorweg-Nijman, JJG, Vreuls, RCFM, Jira, PE, van Trotsenburg, ASP, Bakker, B, Schroor, EJ, Pilon, JW, Wit, JM, Drop, SLS & Hokken-Koelega, ACS 2009, 'Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome', Journal of Clinical Endocrinology & Metabolism, vol. 94, no. 11, pp. 4205-15. https://doi.org/10.1210/jc.2009-0454

Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome. / de Lind van Wijngaarden, Roderick F A; Siemensma, Elbrich P C; Festen, Dederieke A M et al.
In: Journal of Clinical Endocrinology & Metabolism, Vol. 94, No. 11, 11.2009, p. 4205-15.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome

AU - de Lind van Wijngaarden, Roderick F A

AU - Siemensma, Elbrich P C

AU - Festen, Dederieke A M

AU - Otten, Barto J

AU - van Mil, Edgar G A H

AU - Rotteveel, Joost

AU - Odink, Roelof J H

AU - Bindels-de Heus, G C B Karen

AU - van Leeuwen, Mariëtte

AU - Haring, Danny A J P

AU - Bocca, Gianni

AU - Houdijk, E C A Mieke

AU - Hoorweg-Nijman, J J Gera

AU - Vreuls, René C F M

AU - Jira, Petr E

AU - van Trotsenburg, A S Paul

AU - Bakker, Boudewijn

AU - Schroor, Eelco J

AU - Pilon, Jan Willem

AU - Wit, Jan M

AU - Drop, Stenvert L S

AU - Hokken-Koelega, Anita C S

PY - 2009/11

Y1 - 2009/11

N2 - BACKGROUND: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects.OBJECTIVES: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters.SETTING: We conducted a multicenter prospective trial.DESIGN: Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)).RESULTS: Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids.CONCLUSIONS: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.

AB - BACKGROUND: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects.OBJECTIVES: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters.SETTING: We conducted a multicenter prospective trial.DESIGN: Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)).RESULTS: Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids.CONCLUSIONS: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.

KW - Adipose Tissue/anatomy & histology

KW - Birth Weight

KW - Blood Pressure

KW - Body Height

KW - Body Weight

KW - Bone Density

KW - Child

KW - Child, Preschool

KW - Drug Administration Schedule

KW - Fasting

KW - Human Growth Hormone/administration & dosage

KW - Humans

KW - Insulin-Like Growth Factor Binding Protein 3/blood

KW - Insulin-Like Growth Factor I/metabolism

KW - Prader-Willi Syndrome/drug therapy

KW - Prospective Studies

KW - Safety

U2 - 10.1210/jc.2009-0454

DO - 10.1210/jc.2009-0454

M3 - Article

C2 - 19837938

SN - 0021-972X

VL - 94

SP - 4205

EP - 4215

JO - Journal of Clinical Endocrinology & Metabolism

JF - Journal of Clinical Endocrinology & Metabolism

IS - 11

ER -

Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome

Abstract

Keywords

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